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Rhoh deficiency reduces peripheral T‐cell function and attenuates allogenic transplant rejection
Open accessAbstract
Rhoh is a hematopoietic system‐specific GTPase. Rhoh‐deficient T cells have been shown to have a defect in TCR signaling manifested during their thymic development. Our aims were to investigate the phenotype of peripheral Rhoh‐deficient T cells and to explore in vivo the potential benefit of Rhoh deficiency in a clinically relevant situation, in which T‐cell inhibition is desirable. In murine allogenic kidney transplantation, Rhoh deficiency caused a significant 75% reduction of acute and chronic transplant rejection accompanied by 75% lower alloantigen‐specific antibody levels and significantly better graft function. This effect was independent of the lower T‐cell numbers in Rhoh‐deficient recipients, because injection of equal numbers of Rhoh‐deficient or control T cells into kidney transplanted mice with SCID led again to a significant 60% reduction of rejection. Mixed lymphocyte reaction revealed that the weaker alloreactivity was associated with a 85% lower cytotoxicity and a 50–80% lower cytokine release in Rhoh‐deficient T cells without an influence on the secretion itself. Antigen uptake and presentation in DC were unaffected by Rhoh deficiency. These findings stress the importance of Rhoh for the function of peripheral T cells.
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TL;DR
Rhoh deficiency in mice attenuates acute and chronic kidney allograft rejection and improves graft function, largely through intrinsic defects in peripheral T-cell activation, cytokine release, and cytotoxicity rather than altered dendritic cell function or lower T-cell numbers alone. The paper proposes Rhoh as a potential target for suppressing T-cell-mediated transplant rejection.
Key findings
- In murine allogenic kidney transplantation, Rhoh deficiency caused a significant 75% reduction of acute and chronic transplant rejection, 75% lower alloantigen-specific antibody levels, and significantly better graft function.
- When equal numbers of Rhoh-deficient or control T cells were injected into kidney-transplanted SCID mice, Rhoh-deficient T cells still caused a significant 60% reduction of rejection, indicating the effect was not solely due to lower peripheral T-cell numbers.
- Mixed lymphocyte reaction showed 85% lower cytotoxicity and 50–80% lower cytokine release in Rhoh-deficient T cells, without an influence on secretion itself; antigen uptake and presentation by dendritic cells were unaffected.
- Rhoh-deficient T cells showed weaker CD69 upregulation, cytokine secretion, proliferation, and cytotoxicity after TCR stimulation, but no general secretory defect after TCR-independent PMA/A23187 stimulation.
Methods
- Allogenic BALB/c→C57BL/6 kidney transplantations were performed in bilaterally nephrectomized Rhoh-deficient and control recipients, with syngenic C57BL/6→C57BL/6 transplants as controls; grafts were evaluated at days 7, 21, and 42. SCID recipients received equal numbers (1×10^7) of purified Rhoh-deficient or control T cells immediately after transplantation.
- In vitro assays included mixed lymphocyte reactions with equal T cells and T cell-depleted BALB/c stimulators, TCR-dependent stimulation with plate-bound anti-CD3 ± anti-CD28, TCR-independent stimulation with PMA and Ca²⁺ ionophore A23187, cytotoxicity assays, BMDC antigen uptake/presentation assays, flow cytometry, and cytokine bead arrays.
- Histology, immunohistochemistry/immunofluorescence, creatinine clearance, and alloreactive antibody titers were assessed; statistical comparisons used two-tailed unpaired Student’s t-test or Mann-Whitney test, with p<0.05 considered significant.
Limitations
- The paper states that a deranged mast cell phenotype cannot be ruled out completely as contributing to ameliorated rejection, although SCID experiments with wild-type myeloid cells indicated mast cells were not a prominent contributor.
- The paper does not include a dedicated limitations section; evident limitations include the use of a mouse renal allograft model without immunosuppressive therapy, global Rhoh deficiency rather than T-cell-specific deletion, and heterozygous Rhoh+/− controls rather than wild-type controls (though the paper states their phenotype did not differ from wild-type).
- The mechanistic in vitro assays rely on purified splenic T cells and BMDC, so the findings may not fully capture all cell-cell interactions in the transplant microenvironment.
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48 Own result · 21 Sources not found · 10 Own interpretation · 5 Own method
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In the paper
“Rhoh-deficient T cells showed a significantly reduced upregulation of the surface activation marker CD69 (Fig. 7A).”
§ Rhoh deficiency reduces peripheral T-cell function and attenuates allogenic transplant rejection > Rhoh-deficient T cells show a weaker response to alloantigens and less cytotoxicity in vitro
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This also held true during a costimulation with anti-CD28 antibodies (Fig. 8C).”
§ Rhoh deficiency reduces peripheral T-cell function and attenuates allogenic transplant rejection > TCR signaling, but not the cytokine secretion per se, is disturbed in Rhoh-deficient T cells
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In Rhoh-deficient recipients, the tubulointerstitial inflammation remained significantly lower (Figs.1A and 3)”
§ Rhoh deficiency reduces peripheral T-cell function and attenuates allogenic transplant rejection > Rhoh deficiency diminishes acute and chronic transplant rejection
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This was also paralleled by better organ function (Fig. 10H).”
§ Rhoh deficiency reduces peripheral T-cell function and attenuates allogenic transplant rejection > Attenuated rejection in Rhoh-deficient mice is not a consequence of their lower T-cell numbers
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Antigen uptake and presentation in DC were unaffected by Rhoh deficiency.”
§ Rhoh deficiency reduces peripheral T-cell function and attenuates allogenic transplant rejection > Abstract
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 23
- Probably not a substantial claim. 15
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Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The fact that TCR signaling is critically influenced by RhoH is further supported by the observation that in the absence of RhoH allogeneic kidney transplant rejection is reduced in vivo and alloreactivity is weaker in vitro74.”
From Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders (2013) · cites this paper as [74]
In the citing paper
“The fact that TCR signaling is critically influenced by RhoH is further supported by the observation that in the absence of RhoH allogeneic kidney transplant rejection is reduced in vivo and alloreactivity is weaker in vitro74.”
From Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders (2013) · cites this paper as [74]
In the citing paper
“In the spleen and lymph nodes of Rhoh -/-mice, the frequency of naive T cells is low, whereas that of memory T cells is high (34,44).”
From Human RHOH deficiency causes T cell defects and susceptibility to EV-HPV infections (2012) · cites this paper as [44]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Rhoh deficiency reduces peripheral T-cell function and attenuates allogenic transplant rejection > Statistical analysis
“Ã po0.5, ÃÃ po0.01 and ÃÃÃ po0.001.”
§ Rhoh deficiency reduces peripheral T-cell function and attenuates allogenic transplant rejection > Statistical analysis
“Differences were considered significant for po0.05.”
Citations
Cites
Etienne-Manneville, S., & Hall, A. (2002) · Nature · doi:10.1038/nature01148 · Cited by 4,201
Lutz, M. B., Kukutsch, N. A., Ogilvie, A. L. J., Rößner, S., Koch, F., Romani, N., & Schuler, G. (1999) · Journal of Immunological Methods · doi:10.1016/s0022-1759(98)00204-x · Cited by 2,972
A severe combined immunodeficiency mutation in the mouse
Bosma, G. C., Custer, R. P., & Bosma, M. J. (1983) · Nature · doi:10.1038/301527a0 · Cited by 2,230
Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas
Pasqualucci, L., Neumeister, P., Goossens, T., Nanjangud, G., Chaganti, R. S. K., Küppers, R., & Dalla-Favera, R. (2001) · Nature · doi:10.1038/35085588 · Cited by 1,032
The SCID Mouse Mutant: Definition, Characterization, and Potential Uses
Bosma, M. J., & Carroll, A. M. (1991) · Annual Review of Immunology · doi:10.1146/annurev.iy.09.040191.001543 · Cited by 770
Antigen recognition by H-2-restricted T cells. I. Cell-free antigen processing.
Shimonkevitz, R. P., Kappler, J. W., Marrack, P., & Grey, H. M. (1983) · The Journal of Experimental Medicine · doi:10.1084/jem.158.2.303 · Cited by 681
Karttunen, J. T., Sanderson, S., & Shastri, N. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.13.6020 · Cited by 420
Proliferative Assays for T Cell Function
Kruisbeek, A. M., Shevach, E. M., & Thornton, A. M. (2004) · Current Protocols in Immunology · doi:10.1002/0471142735.im0312s60 · Cited by 154
Li, X., Bu, X., Lu, B., Avraham, H., Flavell, R. A., & Lim, B. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.4.1158-1171.2002 · Cited by 153
Preudhomme, C., Roumier, C., Hildebrand, M. P., Dallery-Prudhomme, E., Lantoine, D., Laï, J. L., Daudignon, A., Adenis, C., Bauters, F., Fenaux, P., et al. (2000) · Oncogene · doi:10.1038/sj.onc.1203521 · Cited by 135
Cited by
Human RHOH deficiency causes T cell defects and susceptibility to EV-HPV infections
Crequer, A., Troeger, A., Patin, E., Ma, C. S., Picard, C., Pedergnana, V., Fieschi, C., Lim, A., Abhyankar, A., Gineau, L., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci62949 · Cited by 159
Actin cytoskeletal defects in immunodeficiency
MOULDING, D. A., Record, J., Malinova, D., & Thrasher, A. J. (2013) · Immunological Reviews · doi:10.1111/imr.12114 · Cited by 136
Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders
Troeger, A., & Williams, D. A. (2013) · Experimental Cell Research · doi:10.1016/j.yexcr.2013.07.002 · Cited by 73
Porubský, Š., Speak, A. O., Salio, M., Jennemann, R., Bonrouhi, M., Zafarulla, R., Singh, Y., Dyson, J., Luckow, B., Lehuen, A., et al. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1201483 · Cited by 48
Self-citationCombined Immunodeficiencies with Nonfunctional T Lymphocytes
Notarangelo, L. D. (2014) · Advances in immunology · doi:10.1016/b978-0-12-800100-4.00004-0 · Cited by 48
Rho GTPases in kidney physiology and diseases
Steichen, C., Hervé, J. C., Hauet, T., & Bourmeyster, N. (2021) · Small GTPases · doi:10.1080/21541248.2021.1932402 · Cited by 40
Glucosylceramide Synthase Is Involved in Development of Invariant Natural Killer T Cells
Popović, Z. V., Rabionet, M., Jennemann, R., Krunic, D., Sandhoff, R., Gröne, H., & Porubský, Š. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00848 · Cited by 27
Self-citationPartial defects of T-cell development associated with poor T-cell function
Notarangelo, L. D. (2013) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.01.020 · Cited by 22
Suppression of Chronic Damage in Renal Allografts by Liver X Receptor (LXR) Activation
Kiss, É., Popovic, Z., Bedke, J., Wang, S., Bonrouhi, M., Gretz, N., Stettner, P., Teupser, D., Thiery, J., Porubský, Š., et al. (2011) · American Journal Of Pathology · doi:10.1016/j.ajpath.2011.03.019 · Cited by 22
Self-citationRas Homolog Family Member H (RHOH) Deficiency
Nelson, R. P. (2019) · Springer eBooks · doi:10.1007/978-1-4614-9209-2_106-1
Ras Homolog Family Member H (RHOH) Deficiency
Nelson, R. P. (2020) · Springer eBooks · doi:10.1007/978-1-4614-8678-7_106
A small GTPase, RHOH, is upregulated in the uterus during miscarriage in human and mouse model
Verma, R. K., Sarkar, S., Sankhwar, P., Tripathi, S., Chaubey, P., & Jha, R. K. (2026) · Placenta · doi:10.1016/j.placenta.2026.07.002
Metadata
- Authors
- Porubsky, S., Wang, S., Kiss, E., Dehmel, S., Bonrouhi, M., Dorn, T., Luckow, B., Brakebusch, C., & Gröne, H.
- Affiliations
- German Cancer Research Center (DE)
- Ludwig-Maximilians-Universität München (DE)
- University of Copenhagen (DK)
- Corresponding author
- Gröne, Hermann‐Josef
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2010-11-11
- Volume
- 41
- Issue
- 1
- Pages
- 76-88
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W2160701423
- Semantic Scholar
- d672447d92ffb1da03c8d82d2215aa16b2da6d37
- Cited by
- 13
- References
- 30
- Citations by year
- 2026: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2017: 1 · 2014: 1 · 2013: 3 · 2012: 2
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- European Commission (LSHB-CT-2005-518167)
- Deutsche Forschungsgemeinschaft (GRK 438, SFB405)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- RhoH, Rho GTPases, peripheral T cells, allogeneic kidney transplantation, graft rejection, alloreactivity, cytotoxicity, cytokine production, T cell suppression, dendritic cell antigen presentation, mixed lymphocyte reaction, graft function
- MeSH terms
- Acute Disease, Animals, Antibodies, Chronic Disease, Dendritic Cells, Graft Rejection, Isoantigens, Lymphocyte Culture Test, Mixed, Male, Mice, Inbred BALB C, Mice, Mutant Strains, T-Lymphocytes, Transcription Factors, Kidney Transplantation, Cytokines, Mice, SCID, Antigen Presentation, rho GTP-Binding Proteins, Mice
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