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Anti-CD2 monoclonal antibodies alter cell-mediated immunity in vivo

J S Bromberg1, K D Chavin, P Altevogt

  • 1Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia.

Transplantation
|January 1, 1991
PubMed

Insights

Anti-CD2 monoclonal antibody (mAb) treatment suppresses cell-mediated immunity by altering T-cell receptor expression, impacting both CD4+ and CD8+ T cells without depleting them.

Area of Science:

  • Immunology
  • Cellular Biology
  • Infectious Disease Research

Background:

  • CD2 is a cell surface glycoprotein expressed on T lymphocytes.
  • Its precise role in cell-mediated immunity in vivo remains to be fully elucidated.
  • Understanding CD2's function is crucial for developing targeted immunotherapies.

Purpose of the Study:

  • To investigate the role of CD2 in cell-mediated immunity using an anti-CD2 monoclonal antibody (mAb).
  • To determine the impact of anti-CD2 mAb administration on T cell responses in vivo.
  • To elucidate the mechanism by which anti-CD2 mAb exerts its immunosuppressive effects.

Main Methods:

  • Intravenous administration of anti-murine CD2 mAb 12-15 in vivo.
  • Assessment of contact sensitivity response to trinitrophenyl (TNP) hapten.
  • Evaluation of T cell priming and generation of TNP-specific cytotoxic T lymphocytes (CTLs) in vitro.
  • Analysis of primary, alloantigen-specific CTL development and mixed lymphocyte reaction (MLR).
  • Flow cytometry (FACS) analysis for cell surface marker expression (CD2, CD8, CD3, CD4).

Main Results:

  • Anti-CD2 mAb administration diminished contact sensitivity and inhibited in vivo priming for secondary CTL responses.
  • Immunosuppressive effects were observed when mAb was administered during both early (afferent) and later (efferent) phases of immune response.
  • A dose-dependent relationship was established between anti-CD2 mAb dosage and immunosuppression.
  • Inhibition of primary CTL development occurred without altering the MLR, suggesting a specific effect on CTL generation.
  • FACS analysis revealed significant CD2 downmodulation on T cells, with minor effects on CD8 and no change in CD3 or CD4.

Conclusions:

  • CD2 plays a significant role in various aspects of cell-mediated immunity, affecting both CD4+ and CD8+ effector T cells.
  • Anti-CD2 mAb functions by altering cell surface receptor expression and subsequent responses to antigenic challenge, rather than by cell deletion.
  • These findings highlight CD2 as a potential therapeutic target for modulating T cell-mediated immune responses.

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