CR1(CD35) and CR2(CD21) complement C3 receptors are expressed on normal human thymocytes and mediate infection of thymocytes with opsonized human immunodeficiency virus

Abstract

The present study demonstrates that the C3b receptor CR1 (CD35) and the C3dg/Epstein-Barr virus receptor CR2 (CD21) are expressed by 25% and 70% of normal human thymocytes, respectively. The expression of CR2 extends to both CD1+ and CD1- cells in the thymus. Two subsets of CR2+ thymocytes were defined expressing low and high density of the receptor. The CR2++ subset represented 20% of CR2+ thymocytes and co-expressed the CR1 receptor. CR2++ thymocytes expressed an immature CD1dull, CD3-, CD4dull, CD8-, CD7++ phenotype and included a subpopulation of large cells expressing CD34. Twenty percent of thymocytes expressed the CD21 epitope defined by monoclonal antibody BU32, which is involved in the binding of CD23 to CD21. These observations provide a basis for a role for CD21 in the proliferation and differentiation of thymocytes at early stages of maturation. The functionality of CR1 and CR2 on thymocytes was evidenced by the ability of the receptors to mediate infection of cells with complement-opsonized human immunodeficiency virus (HIV). The results may be relevant to the immunopathogenesis of HIV infection.

Mechanisms of opsonized HIV entry in normal B lymphocytes

“…In addition, the observation that F97-6B3 mAb inhibited virus entry as well as OKB7 Ab suggests that other sites than SRC 1 and 2 are involved in the interactions between HIV and CRs. Inhibition of opsonized HIV infection by CD21 reagents have also been described in T cell lines [18,28], B cell lines [22][23][24] and thymocytes [25]. On B cell lines, Tremblay et al [22] have obtained a complete inhibition of the C'-ADE HIV infection with OKB7 whereas this antibody only induced a partial one in our normal B cells.…”

“…In spite of this activation and of virus opsonization, with anti-HIV antibodies and complement or complement only, HIV seems to be protected from human complement lytic action [17,10]. Non-lysed opsonized HIV may, thus, bind to complement receptors and infect CRs-bearing cells, as described on T cell lines [18], monocytic cell lines [19 21], B cell lines [22][23][24], thymocytes [25], primary monocytes [21], peripheral and tonsil B lymphocytes [8].…”

Complement Opsonization Enhances Friend Virus Infection of B Cells and Thereby Amplifies the Virus-Specific CD8 + T Cell Response

“…Several studies have demonstrated that retroviral infection of complement receptor-expressing cells can be enhanced by complement opsonization (2,5,12,13,16,21,26,28). Since mouse B cells express CR1 and CR2, prolonged interactions of B cells with C-opsonized virions are likely (16).…”

Expression of CD21 and CD23 during Human Fetal Development

“…However, other studies indicate that, although the levels of transcripts for CD21 are comparable between adult peripheral blood T and B cells (29), circulating adult T cells do not express detectable levels of membrane CD21 (29, this study). Still, up to 70% of normal human thymocytes express CD21 (30,31), and it has been suggested that CD21 could have a role in the proliferation and differentiation of T cells in the very early stages of maturation. Thus, the CD21 expression we observed on fetal/neonatal T cells could reflect the immaturity of the T-cell population, indicating recent emigration from the thymus.…”