CD18 is required for intestinal T cell responses at multiple immune checkpoints

Area of Science:

• Immunology
• Gastroenterology
• Cellular Biology

Background:

• Intestinal immune responses to oral antigens are complex.
• The precise role of Leukocyte Function-associated Antigen-1 (LFA-1) in intestinal immunity is not fully understood.
• LFA-1 is known for its role in peripheral T cell trafficking and activation.

Purpose of the Study:

• To investigate the specific functions of LFA-1 in the intestinal immune response.
• To determine the impact of LFA-1 deficiency on T cell migration, activation, and proliferation within the intestinal environment.
• To elucidate the role of LFA-1 in T cell trafficking to the intestinal lamina propria.

Main Methods:

• Adoptive transfer of LFA-1-deficient (CD18(-/-)) CD4(+) T cells into wild-type mice.
• Oral administration of antigen (Ag) to assess T cell responses.
• Analysis of T cell numbers, proliferation, and expression of intestinal-specific trafficking molecules (α(4)β(7), CCR9).

Main Results:

• LFA-1 deficiency reduced Ag-specific T cells in the intestinal lamina propria.
• LFA-1 is essential for optimal CD4(+) T cell proliferation following oral Ag immunization.
• CD18(-/-) T cells showed impaired upregulation of α(4)β(7) and CCR9, affecting trafficking.
• Defective intestinal T cell trafficking persisted even with equivalent activation and differentiation.

Conclusions:

• LFA-1 plays a multifaceted role in intestinal immunity, influencing both early T cell priming and subsequent trafficking.
• CD18 (LFA-1) is critical for T cell migration to the intestinal lamina propria, independent of activation status.
• These findings highlight LFA-1 as a key regulator of T cell homing and function in the gut.