Cross‐talk between Vβ8⁺ and γδ⁺ T lymphocytes in contact sensitivity

Abstract

We have previously reported that T lymphocytes proliferating in vitro to the hapten trinitrochlorobenzene (TNCB) exhibit a very restricted V beta gene usage and response to TNCB is limited to T-cell receptors (TCR) composed of V beta 8.2 in combination with V alpha 3.2, V alpha 8 and V alpha 10. This paper investigates the role played by T lymphocytes expressing the V beta 8.2 gene segment in the contact sensitivity (CS) reaction to TNCB in the intact mouse and in its passive transfer into naive recipient mice. Mice injected with monoclonal antibodies to V beta 8 are unable to develop CS upon immunization with TNCB and 4-day TNCB-immune lymph node cells from mice that had been depleted in vivo or in vitro of V beta 8+ T lymphocytes fail to transfer CS. However, when separated V beta 8+ and V beta 8- cells were used for passive transfer, it was found that V beta 8+ T lymphocytes failed to transfer CS when given alone to recipient mice and a V beta 8- population was absolutely required. Further analysis revealed that within the V beta 8- population, T lymphocytes expressing the gamma delta TCR were fundamental to allow transfer of the CS reaction. These gamma delta cells were found to be antigen non-specific, genetically unrestricted and to rearrange the V gamma 3 gene segment. This indicates that transfer of the CS reaction requires cross-talk between V beta 8+ and gamma delta+ T lymphocytes, thus confirming our previous results obtained using TNCB-specific T-cell lines. Time-course experiments showed that V beta 8+ lymphocytes taken 4-24 days after immunization with TNCB were able to proliferate and produce interleukin-2 (IL-2) in response to the specific antigen in vitro. Similar time-course experiments were then undertaken using the passive transfer of the CS reaction system. The results obtained confirm that TNCB-specific V beta 8+ T lymphocytes are present in the lymph nodes of immunized mice from day 4 to day 24, and reveal that gamma delta+ T lymphocytes are active for a very short period of time, i.e. days 4 and 5 after immunization. In fact, TNCB-specific V beta 8+ cells are able to transfer CS when taken 4-24 days after immunization, providing the accompanying V beta 8- or gamma delta+ T lymphocyte are obtained 4 days after immunization. In contrast, injection of V beta 8+ T lymphocytes together with V beta 8- or gamma delta+ T lymphocytes that had been taken 2 or 6 days after immunization, failed to transfer significant CS into recipient mice. Taken together, our results confirm that cross-talk between V beta 8+ and gamma delta+ T lymphocytes is necessary for full development of the CS reaction and may explain why the CS reaction in the intact mouse lasts up to 21 days after immunization while the ability of immune lymph node cells to transfer CS is limited to days 4 and 5 after immunization.

Antigen Recognition by Human γδ T Lymphocytes

“…5]for a recent review]. Cross-talk between γδ T cells and other cells of the immune system has been shown to modulate humoral [64, 65]and cellular immune responses [66, 67, 68, 69]. Our own in vitro experiments indicate a bidirectional interaction between phosphoantigen-reactive Vγ9/Vδ2 γδ T cells and CD4+ αβ T cells.…”

γδ T Cells Enhance the Expression of Experimental Autoimmune Encephalomyelitis by Promoting Antigen Presentation and IL-12 Production

“…In keeping with this cytotoxicity was the observation that animals receiving nondepleted LNC had higher clinical scores and more prominent lesion activity, the milder scores being associated with less destructive inflammatory lesions in which primary demyelination was the major feature, and the most severe of which were accompanied by widespread CNS lesions that were highly destructive, leading to total loss of nerve fibers. In addition to a proposed effector function, ␥␦ T cells have also been shown to possess important immunoregulatory activities (25)(26)(27)(28)(29)(30)(31)(32). For example, in contact hypersensitivity, the presence of ␥␦ T cells was responsible for transfer of hypersensitivity to naive animals (29).…”

“…However, aside from this effector function, ␥␦ T cells seem to be important regulatory elements of the immune system (25). It has been shown that ␥␦ T lymphocytes are capable of enhancing inflammatory responses in autoimmune diseases, e.g., systemic lupus erythematosus, rheumatoid arthritis (25,26), graft-vs-host disease (27), and delayed-type hypersensitivity (28,29). In addition, ␥␦ T cells are involved in the mechanism of immune tolerance induced by oral (30) or high-dose i.v.…”

CD4 TCRBV CDR3 Analysis in prevalent SLE Cases from two ethnic Groups

“…51,52 Experimental evidence supports the concept of cooperation, or`cross talk' between ab and gd T cells. 53 It follows from these observations that the simultaneous analysis of CDR3 expression in these T cell subsets may improve our knowledge of how these mechanisms contribute to autoimmunity.…”